Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis approach. Results: The patients generally demonstrated inadequate knowledge, particularly of the natural history and staging of CML, the function of TKIs, and the methods used for monitoring the effectiveness of treatment. A number of them also had experiences of withholding, skipping or altering the treatment, mainly due to the life-disturbing adverse drug effects (ADRs), forgetfulness, and religious and social issues. Besides, most of them were found having limited skills in managing the ADRs, and not using prompts as reminders to take the medications. Furthermore, even though nilotinib was generally perceived as better tolerated as compared with imatinib, the inconvenience caused by the need to take it twice daily and on an empty stomach was constantly highlighted by the patients. Conclusion: While TKIs are widely used for CML treatment in Malaysia, the findings have revealed a lack of patient education and awareness, which warrants an integrated plan to reinforce medication adherence.